We evaluated sequential thallium scans, made before and after a period of preoperative chemotherapy, for sixteen patients who had a high-grade sarcoma of bone or soft tissue. The purpose was to determine whether this technique could be used to ascertain accurately the amount of viable tumor as well as to predict the response to chemotherapy. Nine of the ten patients who had a reduced thallium uptake after chemotherapy also had a marked histological response, with necrosis of the tumor of at least 95 per cent. Six patients were seen to have no improvement on the thallium scans, and this finding correlated with necrosis of the tumor of less than 95 per cent. Thallium chloride has been shown to have an affinity for a variety of osteosarcomas and soft-tissue sarcomas. The mechanism of intracellular uptake is one of active transport, which makes thallium chloride a more accurate barometer of the viability of the tumor cells and of metabolic activity than scanning agents that are flow-dependent. We believe that sequential thallium scintigraphy should be used in conjunction with other imaging modalities in the diagnosis, planning of treatment, and follow-up evaluation of patients who have a sarcoma of bone or soft tissue. This technique appears to be useful in the prediction of the histological response of high-grade osteosarcomas and soft-tissue sarcomas to preoperative chemotherapy.